The goal of this research is to understand in greater detail the mechanisms involved in the responses of normal tissues to radiation. The rationale for these studies is based on the current controversy in normal tissue radiobiology concerning the pathogenesis of damage in "late" responding normal tissues, i.e., parenchyma vs. stroma, and the distinction between "late" responding normal tissues and chronic tissue damage. The capacity of irradiated tissues to recover over a period of months to years after initial exposure (as assessed by the amount of residual damage) will be determined with the expectation that late responding normal tissues will recover later and over a longer period of time than acute responding normal tissues, reflecting depletion of a critical cell specific for the response whereas the recovery pattern for chronic tissue damage may be similar for all tissues reflecting a common cellular etiology. Once the recovery profiles have been defined, other studies will investigate the mechanisms underlying any observed changes in retreatment tolerance. The proposed work is divided into three specific aims. The first proposes to determine the recovery pattern for late responding normal tissues and for chronic responses. More specifically, these studies will focus on two late responding normal tissues, kidney and lung, and chronic damage in bowel, skin, and lung. Aim 2 will then investigate the mechanisms underlying any observed changes in retreatment response in previously irradiated tissues. These studies will involve determining oxygen-enhancement ratios for previously irradiated tissues as well as to determine if, when, and in what cell proliferation occurs. Aim 3 will investigate the repair capacity of previously irradiated tissues when recovery is complete or during stimulated proliferation. These studies should increase our understanding of the kinetics of depletion and repopulation of the target cells for late responding normal tissues and for the chronic wave of damage common to all irradiated tissues as well as to provide insight into fundamental processes involved in tissue injury and repair. The potential importance of these studies to clinical radiotherapy is that they should provide radiotherapists with quantitative data and guidelines for designing treatment protocols when retreatment of a previously irradiated site is necessary.